The principal investigator has shown that neutropenia is associated with increased serum levels of colony stimulating factor (CSF). In vivo studies with various preparations of purified CSF suggest that this factor may have a granulopoietic effect in vivo. Moreover, the differentiation of granulocytes in diffusion chambers is markedly inhibited by administration of an antibody against CSF. These ongoing studies will continue to purify large quantities of murine L-cell CSF and determine the effect of this factor in normal and myelosuppressed mice. Recently it has been possible to prepare high titer antibodies directed against pure CSF and to selectively fractionate these antibodies by affinity chromatographic techniques. These pure monospecific antibodies have shown partial inhibition of in vivo granulopoiesis. The purified CSF and anti-CSF will be used to identify CSF producing cells by immunoperoxidase techniques. Moreover, the radioiodinated CSF will be used for binding studies for defining bone marrow stem cell receptors. Further refinements of these techniques should allow for morphologic and functional characterization of the CSF responsive stem cells. Radioiodinated CSF and high titer antiserum have been used to design a sensitive radioimmunoassay. This RIA will be used to determine the extent and type of CSF in murine serum and to evaluate the potential role of high molecular weight serum inhibitors.